Study findings could help develop treatments for Alzheimer’s, Parkinson’s

She's a biologist investigating microbial genomics. He studies protein structures using
electron microscopy. Put them together and their research opens doors.

A unique collaboration between Marie Elliot and Joaquin Ortega, members of the
McMaster Institute for Infectious Disease Research, is providing new insight into the
assembly of 'amyloids' – protein aggregates that are associated with neurodegenerative
diseases like Alzheimer's and Parkinson's.

Elliot, who studies bacterial development, approached Ortega to help with her
biochemical and genetic investigations into amyloids using electron microscopy, a
unique structural method to analyze macromolecular assemblies on a very fine scale.
Using this combined approach they discovered two separate domains within a 'chaplin'
protein (a group of proteins that contribute to the development of Streptomyces
bacteria), that contributes to the ability of this protein to form amyloids.

“This finding advances our understanding of amyloid assembly,” said Elliot, “and
expands the known ways that amyloids can form. This knowledge may ultimately help
to increase our chances of treating amyloid-associated disease.”

“Amyloids are more typically associated with diseases like Alzheimer's and type II
diabetes, and now we have shown that this association is critical for chaplin function,”
said Elliot. “We are interested in understanding the differences between toxic (disease-
causing amyloids), and 'functional amyloids' like the chaplins. To do this, we are
probing the underlying genetic and biochemical factors that control the assembly of
these functional amyloids.”

“These findings have a broad impact on better understanding the role of amyloids and
contribute to new insight in bacterial development,” she said. “Amyloid proteins
typically share common biochemical characteristics, but have diverse sequences and
cellular functions. What makes the chaplins such a powerful model system is that they
have defined biological functions that can be readily assessed and genetically
manipulated.”

Ortega credits the collaborative nature of the IIDR as one reason for the study's success.
The IIDR brings together members from three faculties and eight departments at
McMaster. “These kinds of results reflect the things that can be achieved within the
IIDR,” he said. “It highlights the possibilities of collaborations between groups. Our
expertise is different but it complements each other well and allows us to look at
problems in a new way. In addition, this work shows the quality, drive and motivation of
our trainees at the IIDR. It has been very rewarding to witness how David Capstick and
Ahmad Jomaa, first and second author in this publication, took the initial ideas and
materialized them into high quality data that provide solid foundation to our findings.”

The study, entitled “Dual amyloid domains promote differential functioning of the
chaplin proteins during Streptomyces aerial morphogenesis” received funding from the
Canadian Institutes of Health Research and is published in the Proceedings of the
National Academy of Sciences (PNAS).